676
J. T. Blanchfield et al.
are contraindicated by the analyses of chemical shifts in the
doped spectra.[1] In addition, these diastereomers would be
anticipated to exhibit mass spectra similar to those of 15,
16, 26, and 27. The question remains as to the correct struc-
ture of laurobtusol, but this determination would require the
re-isolation of this material as none of the original sample
remains.[9] Our efforts to deduce an alternative structure for
laurobtusol, for example of the perhydroazulenoid type, have
been unrewarding.
26, and 27 and their EIMS; the mass spectrum of (natural)
laurobtusol (courtesy of Professor S. Caccamese); ORTEP
diagrams of compounds 13, 20, 21, 23, and 12; 1H and
13C NMR spectral traces of (major) isomer 15 showing
signal broadening phenomena; the 100 MHz 13C NMR spec-
trum of the mixture 15, 16, 26, and 27; the 125 MHz 13C
NMR spectrum (C6D6) of the mixture 15, 16, 26, and 27
1
in the region of C1; the 750 MHz H NMR spectrum of
15, 16, 26, and 27 in the high-field region (for C6D6 sol-
vent) showing AX patterns for the cyclopropyl methylene
groups;andspectral, analytical, andphysicaldataofsomekey
intermediates.
Experimental
1a,4,6,6-Tetramethyldecahydrocyclopropa[d]naphthalene-8-ol 15, 16,
26, and 27
Diethylzinc (0.28 mL, 1.0 M in hexane) was slowly added to the allylic
alcohol mixture 11 and 12 (20 mg, 0.10 mmol) in CH2Cl2 (0.5 mL) at
0◦C (ice bath).[10] After stirring for 5 min, CH2I2 (22 µL, 0.27 mmol)
was added dropwise. The cloudy solution was stirred for 3 h while the
reaction mixture was warmed gradually to room temperature. After the
addition of diethyl ether (4 mL), the flask was re-cooled to 0◦C and
saturatedNH4Cl(2 mL)wasadded.Theaqueouslayerwasseparatedand
re-extracted with diethyl ether (3 × 5 mL). The combined organic layers
were washed with brine, dried over MgSO4, concentrated, and subjected
to column chromatography (alumina, 10% diethyl ether/hexane). On the
basis of GCMS analysis, the product (13 mg, 61%) consisted of two
Acknowledgments
The authors are deeply indebted to Professors S. Caccamese
and P. Neri, Universitá di Catania, Italy, for their friendly
and cooperative exchanges of information, and for the copies
of NMR and mass spectra of laurobtusol, to Professor J. C.
Braekman of the Université Libre de Bruxelles, Belgium, for
the mass spectrum of africanol, and to Professor Charette,
Université de Montréal, Canada, for comments on cyclo-
propanation procedures. The GCHRMS of 15, 16, 26, and 27
were very kindly obtained by Dr Stefan Franke and Professor
Dr Wittko Francke of the Institute for Organic Chemistry,
University of Hamburg, Germany, to whom we are most
grateful.
major and two minor isomers.
•
Compound 15 (major isomer) (Found: M+ 222.1974. C15H26
O
•
requires M+ 222.1984). δH (500 MHz) 3.62 (1H, dd, J 6.3, 3.3, H1),
1.72 (1H, dt, J 13.5, 4.1, H4a), 1.66 (2H, m, H7), 1.58 (1H, m, H2),
1.56 (1H, m, H4), 1.54 (1H, m, H5), 1.52 (1H, m, H2), 1.26 (2H, m,
H6), 1.23 (3H, s, H10), 1.07 (1H, dd, J 12.8, 3.8, H4), 1.02 (3H, s, H13),
0.97 (3H, s, H12), 0.79 (3H, d, J 6.8, H11), 0.40 (1H, d, J 4.2, H9),
0.38 (1H, d, J 4.2, H9). δC (125 MHz) 74.0 (C1), 44.6 (C2), 39.1 (C8),
38.0 (C4a), 34.3 (C13), 30.3 (C8a), 29.5 (C3), 29.1 (C12), 28.8 (C5),
28.1 (C7), 26.7 (C6), 22.4 (C10), 21.6 (C9), 20.5 (C8), 15.6 (C11). m/z
(EIMS) 222 (1%, M+•), 207 (2), 204 (7), 189 (9), 165 (15), 151 (13),
References
[1] S. Caccamese, V. Amico, P. Neri, M. Foti, Tetrahedron 1991,
47, 10101. doi:10.1016/S0040-4020(01)96059-4
[2] Some of this work is described in the following theses:
(a) J. Blanchfield, Ph.D. Thesis 1996 (University of Queensland:
Brisbane).
133 (13), 125 (83), 107 (31), 93 (36), 79 (36), 69 (38), 55 (68), 41 (100).
•
Compound 16 (major isomer) (Found: M+ 222.1995. C15H26
O
•
requires M+ 222.1984). δH (500 MHz) 3.47 (1H, t, J 3.0, H1), 1.80
(1H, ddd, J 13.4, 4.0, 2.5, H7eq), 1.69 (1H, m, H2), 1.58 (1H, m, H7ax),
1.65 (1H, m, H4), 1.45 (1H, m, H2), 1.40 (1H, m, H6ax), 1.25 (3H, s,
H10), 1.17 (1H, m, H4a), 1.06 (3H, s, H13), 0.94 (3H, s, H12), 0.86 (1H,
m, H6), 0.81 (3H, d, J 7.0, H11), 0.39 (1H, d, J 4.2, H9), 0.27 (1H, d,
J 4.2, H9). δC (125 MHz) 76.7 (C1), 42.0 (C4a), 41.6 (C2), 40.9 (C4),
36.4 (C5), 34.2 (C13), 32.5 (C7), 31.0 (C12), 30.8 (C8a), 30.0 (C6),
28.5 (C3), 25.0 (C9), 23.0 (C8), 22.9 (C10), 21.1 (C11). m/z (EIMS)
222 (2%, M+•), 207 (3), 204 (5), 189 (8), 165 (19), 151 (12), 133 (11),
125 (95), 107 (35), 93 (36), 79 (35), 69 (38), 55 (75), 41 (100).
(b) S. Chow, Ph.D. Thesis 2004 (University of Queensland:
Brisbane), submitted.
Professor Ho (National Chiao Tung University, Taiwan) briefly
outlined in 1998 a proposed route to laurobtusol resembling our
conjugate addition–aldolization procedure shown in Scheme 2.
T. L. Ho, S. T. Yeh, 216th ACS National Meeting 1998 (ACS:
Boston, MA).
Professor Ho informed W.K. in March 2003 that his group
had acquired two stereoisomers of laurobtusol, and a possible
intermediate that could be converted into racemic laurobtusol.
None of this work has been published.
Compounds 26/27 (minor isomer), see Table 1 for key NMR data
(Found: M+• 222.1967. C15H26O requires M+• 222.1984). m/z (EIMS)
222 (1%, M+•), 207 (3), 204 (8), 189 (7), 165 (52), 151 (13), 138 (22),
125 (45), 107 (30), 93 (36), 79 (31), 69 (35), 55 (93), 41 (100).
Compounds 27/26 (minor isomer), see Table 1 for key NMR data
(Found: M+• 222.1990. C15H26O requires M+• 222.1984). m/z (EIMS)
222 (5%, M+•), 207 (13), 204 (4), 189 (10), 165 (75), 151 (20), 138
(41), 125 (60), 107 (42), 93 (40), 79 (39), 69 (40), 55 (67), 41 (100).
[3] S. Winstein, J. Sonnenberg, L. de Vries, J. Am. Chem. Soc.
1961, 83, 3235.
[4] J. Tsuji, I. Shimizu, K. Yamamoto, Tetrahedron Lett. 1976, 2975,
and references therein. doi:10.1016/S0040-4039(01)85504-0
[5] S. E. Denmark, J. P. Edwards, J. Org. Chem. 1991, 56, 6974.
[6] G. A. Molander, S. C. Harring, J. Org. Chem. 1989, 54, 3525.
[7] E. J. Corey, M. Chaykovsky, J. Am. Chem. Soc. 1965, 87, 1353.
[8] C. R. Johnson, J. P. Adams, M. P. Braun, C. B. W. Senanayake,
Tetrahedron Lett. 1992, 33, 919. doi:10.1016/S0040-4039(00)
91576-4
The following material is available from the author or, until
July 2009, the Australian Journal of Chemistry: general
experimental procedures; a GC trace showing isomers 15, 16,
[9] S. Caccamese, unpublished results.
[10] J. Furukawa, N. Kawabata, J. Nishimura, Tetrahedron 1968, 24,
53. doi:10.1016/0040-4020(68)89007-6